Valve for aerosol container

ABSTRACT

A valve for an aerosol container suitable for use in dispensing a quantity of the contents thereof is disclosed. The valve components comprise a fluorinated polymer and/or a fluorinated coating which have been found to reduce drug deposition in the valve.

RELATED APPLICATIONS

[0001] This application is a continuation of application Ser. No.09/646,270, allowed, which is the National Stage of InternationalApplication No. PCT/EP99/01757, filed Mar. 17, 1999, which claimspriority from Application No. 9805938.9, filed in Great Britain on Mar.19, 1998.

[0002] The invention provides a valve for an aerosol container suitablefor use in dispensing a quantity of the contents thereof and which maybe used in the treatment of asthma and other ailments. In particular,the invention provides a valve for a metered dose inhaler suitable foruse in dispensing metered doses of medicaments.

[0003] Containers for aerosol formulations commonly comprise a vial body(can) coupled to a valve. The valve comprises a valve stem through whichthe formulations are dispensed. Generally the valve includes a rubbervalve seal intended to allow reciprocal movement of the valve stem whichprevents leakage of propellant from the container. Metered dose inhalerscomprise a valve which is designed to deliver a metered amount of anaerosol formulation to the recipient per actuation. Such a meteringvalve generally comprises a metering chamber which is of a set volumewhich aims to administer per actuation an accurate, predetermined dose.

[0004] Suitable valves for use in the invention are available frommanufacturers well known in the aerosol industry, for example, fromValois, France (eg. DF10, DF30, DF60), Bespak plc, United Kingdom (eg.BK300, BK356, BK357) and 3M-Neotechnic Limited, United Kingdom (eg.Spraymiser™). The metering valves are used in association withcommercially available canisters such as aluminium canisters, suitablefor delivering pharmaceutical aerosol formulations.

[0005] Aerosol formulations which are generally used comprise asuspension of a medicament, one or more liquid propellants, optionallywith a co-propellant, and optionally an adjuvant such as a solvent or asurfactant, though the invention may be applicable to the dispensing ofany aerosol formulation. The aerosol formulation is under pressure inthe canister.

[0006] It has been found that conventional aerosols, particularlymetered dose inhalers, suffer impaired performance due to the depositionof drug particles in the valve component, particularly in the meteringchamber. This leads to a high occurrence of inconsistency in the dosesof drug being administered which becomes particularly acute overincreasing numbers of actuations. The problem of drug deposition inconventional aerosols is particularly exacerbated when excipient-freeaerosol formulations are used based on the hydrofluoro alkane (HFA)propellants 134a and 227. It has further been found that drug depositionincreases with storage of the aerosol, particularly when the aerosol isstored at high temperature and/or high humidity.

[0007] The invention provides a valve for an aerosol in which there issignificantly reduced drug deposition compared with conventionallyavailable valves when the valve is used in aerosols comprising anaerosol formulation for inhalation. In particular, the inventionprovides a metering valve having a metering chamber in which there issignificantly reduced drug deposition.

[0008] Accordingly the invention relates to a valve for an aerosolcontainer for dispensing a suspension or solution of a substance in aliquid propellant contained therein, wherein the valve comprises a valvebody defining a chamber, a transfer passage through which a quantity ofsubstance to be dispensed can pass from the container into the chamber,and dispensing means which allows the substance to be dispensed, inwhich the chamber comprises a fluorinated polymer.

[0009] The invention further provides an aerosol container whichcomprises a valve according to the invention, and an inhalation device,preferably a metered dose inhaler, which comprises the aerosolcontainer.

[0010] The invention further provides a method of reducing drugdeposition in a metering chamber for use in a metered dose inhaler bythe use of a fluorinated polymer according to the invention.

[0011] The invention further provides a valve for an aerosol containeras described hereinabove in which the surface of the chamber, forexample, the metering chamber, in contact with the substance to bedispensed is coated with a fluorinated material including fluorinecoatings, plastics materials comprising fluorinated materials etc.

[0012] The fluorinated coating is preferably a plasma coating, forexample, a CF4 plasma coating. Preferably the fluorinated plasma coatingCF4 is applied to the metering chamber of a metering valve which may bemade from any conventionally used plastics material such as Acetal,polyester, etc. The plasma coating may consist of a fluorinated polymerlaid down on the surface of the valve component, preferably the chamber,by polymerisation or direct modification of the material surface byinterchange of hydrogen ions in the material with fluorine ions. Thecoating process typically takes place in a vacuum at ambienttemperature. The components to be coated are placed inside a chamberwhich is evacuated. The fluorine monomer or fluorine source isintroduced into the chamber at a controlled rate. The plasma is ignitedwithin the chamber and maintained for a given time at a chosen powersetting. At the end of the treatment the plasma is extinguished, thechamber flushed and the products retrieved. In the polymerisationprocess, a thin layer of plasma polymer will be bonded to the surface ofthe chamber, preferably a metering chamber, or any other surface of thevalve to be coated.

[0013] The fluorinated polymer may be selected from any conventionallyused fluorinated polymer/copolymer or mixtures thereof or mixture of thefluorinated polymer in combination with non-fluorinated polymersconventionally used in the manufacture of valves, such as acetal,polyester (PBT) as well as polymer blends with, for example, stainlesssteel (eg. PBT/stainless steel blend (PDX WO96082)), etc. Examples ofsuitable fluorinated polymers include polytetrafluoroethylene (PTFE),ethylenetetrafluoroethylene (ETFE), polyvinyldienefluoride (PVDF),perfluoroalkoxyalkane (PFA), polyvinylfluoride (PVF),polychlorotrifluoroethylene (PCTFE), fluorinated ethylenepropylene (FEP)etc. Suitable copolymers include copolymers of tetrafluoroethylene (TFE)with PFA, TFE with hexafluoropropylene (HFP) (available as FEP 6107 andFEP 100 from DYNEON), VDF with HFP (commercially available as Viton A),TFE with perfluoro(propyl vinyl ether) (available as PFA 6515N fromDYNEON), a blend of TFE, hexafluoropropylene and vinylidene fluoride(available commercially as THV 200G from DYNEON), etc.

[0014] It should be noted, however, that any conventionally availablepolymer, copolymer or mixture thereof which comprises a fluorinatedpolymer and which can be used to make the valve for use in an inhaleraccording to the invention will be suitable. Examples of mixtures ofpolymers and/or copolymers comprise, for example, up to 80% by weightfluorinated polymer, optionally up to 40% by weight fluorinated polymer,optionally up to 20% by weight fluorinated polymer or optionally up to5% by weight of fluorinated polymer. Preferably, fluorinated polymersselected from PTFE, PVF and PCTFE are used as mixtures withnon-fluorinated polymers. For example a suitable material is HOSTAFORMX329™ (Hoechst) which is a 5% PTFE/Acetal blend, HOSTAFORM C9021TF whichis a 20% PTFE/Acetal blend, PTFE/PBT blends (for example, LNP WL4040),PTFE/PBT/silicone blends (for example, LNP WL4540).

[0015] The fluorinated polymers and mixtures thereof used in theinvention can be moulded in any conventional manner, for example, byinjection moulding, plastic moulding etc.

[0016] According to a preferred embodiment of the invention, the valveis a metering valve comprising a metering chamber, a transfer passagethrough which a quantity of substance to be dispensed can pass from thecontainer into the metering chamber, wherein in the first position thedispensing passage is isolated from the metering chamber and themetering chamber is in communication with the container via the transferpassage, and in the second position the dispensing passage is incommunication with the metering chamber and the transfer passage isisolated from the metering chamber.

[0017] Medicaments which may be administered in the aerosolformulations, suitably suspended in a liquid propellant, include anydrugs useful in inhalation therapy which may be present in a form whichis substantially completely insoluble in the selected propellant system.The aerosol formulation, if desired, may comprise one or more activeingredients. Aerosols comprising two active ingredients in aconventional propellant system are known for the treatment ofrespiratory disorders such as asthma. Appropriate medicaments may thusbe selected from, for example, analgesics, e.g. codeine,dihydromorphine, ergotamine, fentanyl or morphine; anginal preparations,e.g. dilitiazem; antiallergics, e.g. cromolyn, cromoglycate ornedocromil; antibiotics, e.g. cephalosporins, penicillins, streptomycin,sulphonamides or tetracyclines; antihistamines, e.g. methapyrilene;anti-inflammatories, e.g. beclomethasone, flunisolide, fluticasone,tipredane, budesonide, triamcinolone acetonide; antitussives, e.g.noscapine; bronchodilators, e.g. ephedrine, epinephrine, fenoterol,formoterol, isoprenaline, isoproterenol, metaprotemol, phenylephrine,phenylpropanolamine, pirbuterol, repoterol, rimiterol, salbutamol,salmeterol, terbutaline or(-)-4-amino-3,4-dichloro-α-[[[6-[2-(2-pyridinyl)ethoxy]hexyl]amino]methyl]benzenemethanol;diuretics, e.g. amiloride; antichloinergics e.g. ipratropium bromide;hormones, e.g. cortisone, hydrocortisone or prednisolone; andtherapeutic proteins and peptides, e.g. glucagon or insulin. It will beclear to a person skilled in the art that, where appropriate, themedicaments will be used in the form of salts (e.g. as alkali metal oramine salts or as acid addition salts) or as esters (e.g. lower alkylesters) or as solvates (eg hydrates) to optimise the activity and/orstability of the medicament and/or to minimise the solubility of themedicament in the propellant.

[0018] Preferably the medicament is selected from bronchodilators andanti-inflammatory steroids of use in the treatment of asthma byinhalation therapy, including salbutamol (e.g. as the sulphate),salmeterol (e.g. as the hydroxynaphthoate known as salmeterolxinafoate), beclomethasone dipropionate or a solvate thereof,fluticasone propionate or(-)-4-amino-3,5-dichloro-α-[[[6-[2-(pyridinyl)ethoxy]hexyl]amino]methyl]benzenemethanol and mixtures thereof.

[0019] The particle size of the particulate medicament should be such asto permit inhalation of substantially all of the medicament into thelungs upon administration of the aerosol formulation and will thusdesirably be less than 20 microns, preferably in the range 1 to 10microns, e.g. 1 to 5 microns. The particle size of the medicament or themedicament together with the excipient may be reduced by conventionalmeans, for example by milling, micronisation, spray-drying or controlledrecrystallization.

[0020] The final aerosol formulation desirably contains 0.0005-10% w/w,preferably 0.0005-5% w/w, especially 0.01-1.0% w/w, of medicamentrelative to the total weight of the formulation.

[0021] Examples of aerosol propellants for the aerosol formulationsinclude CCl₃F (propellant 11) in admixture with CCl₂F₂ (propellant 12)CF₂Cl.CF₂Cl (propellant 14), however, due to the ozone-depleting effectsbelieved to be associated with such propellants, the valve for anaerosol container of the invention is more suitably used with aerosolformulations which comprise so called “ozone-friendly” propellants.

[0022] Preferably, the propellants are selected from hydrogen-containingchlorofluorocarbons and fluorocarbons and a number of medicinal aerosolformulations using such propellant systems have been disclosed in, forexample, EP 0372777, WO91/04011, WO91/11173, WO91/11495, WO91/14422,WO92/00061, WO92/00062 and WO92/00107.

[0023] Suitable propellants include, for example, C₁₋₄hydrogen-containing chlorofluorocarbons such as CH₂ClF, CClF₂CHClF,CF₃CHClF, CHF₂CClF₂, CHClFCHF₂, CF₃CH₂Cl and CClF₂CH₃; C₁₋₄hydrogen-containing fluorocarbons such as CHF₂CHF₂, CF₃CH₂F, CHF₂CH₃ andCF₃CHFCF₃ and C₁₋₄ perfluorocarbons such as CF₃CF₃ and CF₃CF₂CF₃.

[0024] Where mixtures of the fluorocarbons or hydrogen-containingchlorofluorocarbons are employed they may be mixtures of the aboveidentified compounds or mixtures, preferably binary mixtures, with otherfluorocarbons or hydrogen-containing chlorofluorocarbons for exampleCHClF₂, CH₂F₂ and CF₃CH₃.

[0025] A single fluorocarbon or hydrogen-containing chlorofluorocarbonmay be employed as the propellant. Particularly preferred as propellantsare hydrogen-containing fluorocarbons, especially1,1,1,2-tetrafluoroethane (CF₃CH₂F) (propellant 134a) and1,1,1,2,3,3,3-heptafluoro-n-propane (CF₃CHFCF₃) (propellant 227) or amixture thereof. The propellants are preferably used in the absence ofexcipients and adjuvants, such as solvents and surfactants. As usedherein “substantially free” refers to formulations which contain nosignificant amounts of surfactant, for example, less than 0.0001% byweight based upon the weight of the medicament. However, the inventionalso applies to formulations which include any conventionally usedexcipients, such as, surfactants etc.

[0026] The formulations may be prepared by any conventionally knownprocess, for example, by dispersal of the medicament in the selectedpropellant in an appropriate container, e.g. with the aid of sonication.

[0027] Minimising and preferably avoiding the use of formulationexcipients e.g. surfactants, cosolvents etc. in the aerosol formulationsis advantageous since the formulations may be substantially taste andodour free, less irritant and less toxic than conventional formulations.However, such formulations are associated with a higher degree of drugdeposition on the valve components. The fluorinated valve according tothe invention, particularly the valve having a fluorinated meteringchamber, is preferably used to administer formulations substantiallyfree of excipients which has been found to substantially reduce drugdeposition in the valve.

[0028] The formulations may be filled into canisters suitable fordelivering pharmaceutical aerosol formulations. Canisters generallycomprise a container capable of withstanding the vapour pressure of thepropellant used such as a plastic or plastic-coated glass bottle orpreferably a metal can, for example an aluminium can which mayoptionally be anodised, lacquer- or polymer-coated and/orplastic-coated, which container is closed with a valve according to theinvention.

[0029] Conventional bulk manufacturing methods and machinery well knownto those skilled in the art of pharmaceutical aerosol manufacture may beemployed for the preparation of large scale batches for the commercialproduction of filled canisters. Thus, for example, in one bulkmanufacturing method a metering valve is crimped onto an aluminium canto form an empty canister. The medicament is added to a charge vesseland liquified propellant is pressure filled through the charge vesselinto a manufacturing vessel. The drug suspension is mixed beforerecirculation to a filling machine and an aliquot of the drug suspensionis then filled through the metering valve into the canister. Typically,in batches prepared for pharmaceutical use, each filled canister ischeck-weighed, coded with a batch number and packed into a tray forstorage before release testing.

[0030] Each filled canister may be conveniently fitted into a suitablechannelling device prior to use to form a metered dose inhaler foradministration of the medicament into the lungs or nasal cavity of apatient. Suitable channelling devices comprise for example a valveactuator and a cylindrical or cone-like passage through which medicamentmay be delivered from the filled canister via the metering valve to thenose or mouth of a patient e.g. a mouthpiece actuator.

[0031] A spacer may be placed between the passage and the mouthpiece.Metered dose inhalers are designed to deliver a fixed unit dosage ofmedicament per actuation or “puff”, for example in the range of 10 to5000 microgram medicament per puff.

[0032] According to a further embodiment of the invention, other partsof the inhaler which are also susceptible to drug deposition maycomprise the fluorinated polymer of the invention and/or be coated withthe fluorinated material according to the invention, for example, theactuator into which the filled canister comprising the valve is fittedfor application by the patient. All or part of the actuator, forexample, the valve actuator, mouthpiece actuator etc. may comprise thefluorinated polymer/copolymer or mixtures thereof and/or be coated withthe fluorinated material.

[0033] Administration of medicament may be indicated for the treatmentof mild, moderate or severe acute or chronic symptoms or forprophylactic treatment. It will be appreciated that the precise doseadministered will depend on the age and condition of the patient, theparticular particulate medicament used and the frequency ofadministration will ultimately be at the discretion of the attendantphysician. When combinations of medicaments are employed the dose ofeach component of the combination will in general be that employed foreach component when used alone. Typically, administration may be one ormore times, for example from 1 to 8 times per day, giving for example 1,2, 3 or 4 puffs each time.

[0034] Each valve actuation, for example, may deliver 25 μg, 50 μg, 100μg, 200 μg or 250 μg of a medicament. Typically each filled canister foruse in a metered dose inhaler contains 60, 100, 120 or 200 metered dosesor puffs of medicament.

[0035] The invention will now be described further with reference to theaccompanying drawing in which FIG. 1 is a section through a meteringvalve according to the invention and to the following Examples whichserve to illustrate the invention but are not intended to be limiting.

[0036] A valve according to the invention is shown in FIG. 1 andcomprises a valve body 1 sealed in a ferrule 2 by means of crimping, theferrule itself being set on the neck of a container (not shown) withinterposition of a gasket 3 in a well-known manner.

[0037] The valve body 1 is formed at its lower part with a meteringchamber 4, and it upper part with a sampling chamber 5 which also actsas a housing for a return spring 6. The metering chamber is made atleast in part from a fluorinated polymer and/or a fluorinated coatingaccording to the invention. The words “upper” and “lower” are used forthe container when it is in a use orientation with the neck of thecontainer and valve at the lower end of the container which correspondsto the orientation of the valve as shown in FIG. 1. Inside the valvebody 1 is disposed a valve stem 7, a part 8 of which extends outside thevalve through lower stem seal 9 and ferrule 2. The stem part 8 is formedwith an inner axial or longitudinal canal 10 opening at the outer end ofthe stem and in communication with a radial passage 11. The upperportion of stem 7 has a diameter such that it can slide through anopening in an upper stem seal 12 and will engage the periphery of thatopening sufficiently to provide a seal. Upper stem seal 12 is held inposition against a step 13 formed in the valve body 1 between the saidlower and upper parts by a sleeve 14 which defines the metering chamber4 between lower stem seal 9 and upper stem seal 12. The valve stem 7 hasa passage 15 which, when the stem is in the inoperative position shown,provides a communication between the metering chamber 4 and samplingchamber 5, which itself communicates with the interior of the containervia orifice 26 formed in the side of the valve body 1.

[0038] Valve stem 7 is biased downwardly to the inoperative position byreturn spring 6 and is provided with a shoulder 17 which abuts againstlower stem seal 9. In the inoperative position as shown in FIG. 1shoulder 17 abuts against lower stem seal 9 and radial passage 11 opensbelow lower stem seal 9 so that the metering chamber 4 is isolated fromcanal 10 and suspension inside cannot escape.

[0039] A ring 18 having a “U” shaped cross section extending in a radialdirection is disposed around the valve body below orifice 26 so as toform a trough 19 around the valve body. As seen in FIG. 1 the ring isformed as a separate component having an inner annular contacting rim ofa diameter suitable to provide a friction fit over the upper part ofvalve body 1, the ring seating against step 13 below the orifice 26.However, the ring 18 may alternatively be formed as an integrallymoulded part of valve body 1.

[0040] To use the device the container is first shaken to homogenise thesuspension within the container. The user then depresses the valve stem7 against the force of the spring 6. When the valve stem is depressedboth ends of the passage 15 come to lie on the side of upper stem seal12 remote from the metering chamber 4. Thus a dose is metered within thefluorinated metering chamber. Continued depression of the valve stemwill move the radial passage 11 into the metering chamber 4 while theupper stem seal 12 seals against the valve stem body. Thus, the metereddose can exit through the radial passage 11 and the outlet canal 10.

[0041] Releasing the valve stem causes it to return to the illustratedposition under the force of the spring 6. The passage 15 then once againprovides communication between the metering chamber 4 and samplingchamber 6. Accordingly, at this stage liquid passes under pressure fromthe container through orifice 26, through the passage 15 and thence intothe metering chamber 4 to fill it.

[0042] In the following Examples each aerosol contains a suspension of amedicament in an excipient-free propellant formulation. In each caseaerosols having conventionally available valves made from acetal orpolyester are compared with aerosols having valves according to theinvention in which either the metering chamber is made from fluorinatedethylene polymer or from polyester which has been plasma coated withCF4. In each case, the drug deposition generated through use is measuredand “Dose Through Use” collection regimes are carried out to analyzedoses administered during the life of the inhaler. The formulationtested in each case was an excipient-free propellant formulationcomprising fluticasone propionate and 134a propellant.

[0043] Valve Drug Deposition Method

[0044] The quantity of drug deposited in the valve was measured. Theinterior valve components include the metering chamber, upper stemgasket and the parts of the upper and lower stem, which are within themetering chamber. For deposition performed at the beginning of use (BOU)of the inhaler, 2 testfire and 3 manual actuations are taken valve-downfollowed by 1 manual actuation valve-up to evacuate the meteringchamber. Deposition performed on inhalers at end of use (EOU) has used120 actuation inhalers. Before deposition is performed on theseinhalers, 1 manual actuation valve-down is taken followed by 1 manualactuation valve-up to evacuate the metering chamber.

[0045] The sample preparation for measuring the valve deposition is thesame for both BOU and EOU inhalers. Firstly, the valve stem is washedwith acetonitrile. Then, the inhaler is chilled for five minutes in abath of dry ice and methanol. The valve is removed from the inhaler andthe valve interior components are washed quantitatively withacetonitrile into a 50 ml volumetric flask containing 25 ml water. Thedrug solution was made to volume and the resultant solution assayed forfluticasone propionate by HPLC.

[0046] Dosing Method

[0047] The following method was used to evaluate the dosing for thedifferent valve variants for each experiment. The dose was collected aspairs of actuations at the BOU and EOU of the inhaler.

[0048] Before the dose collection at BOU, 2 testfire and 4 manualactuations were fired to waste valve-down. Actuations 1 and 2 were firedinto a dose trap. The dose trap was washed quantitatively withacetonitrile into a 100 ml volumetric flask containing 50 ml water. Thedrug solution was made to volume and the resultant solution assayed forfluticasone propionate by HPLC.

[0049] After BOU collections, the inhalers have another 116 actuationfired to waste. The inhalers are at EOU. Actuations 119 and 120 werefired into a dose trap. The dose trap was washed quantitatively withacetonitrile into a 100 ml volumetric flask containing 50 ml water. Thedrug solution was made to volume and the resultant solution assayed forfluticasone propionate by HPLC.

EXAMPLE 1

[0050] The EOU interior valve deposition and dosing profile on valveswas investigated with different polymer metering chambers. FluticasonePropionate/Propellant HFA134a Inhalers, 50 microgram, 120 actuation weremanufactured using the DF60 valve (acetal components, different polymermetering chambers and nylon ring). The inhalers were stored for aminimum of 2 weeks before analysis of the drug deposited on valve. Thedeposition and dosing data are presented in Tables 1 and 2. TABLE 1 Drugdeposition in metering chamber Composition of Metering Chamber Amount ofdrug deposition-mg Standard acetal 0.26 Standard polyester 0.28 CF4coated polyester 0.15 FEP 100 0.10 X329 (5% PTFE/acetal blend) 0.18

[0051] TABLE 2 Dosing Data at Actuations 1 + 2/119 + 120 (for a 120 doseproduct) Increase Composition of Actuation Actuation in dose Metering1 + 2 119 + 120 during life of Chamber Dose μg SD Dose μg SD inhaler(μg) Standard acetal 39.6   5% 54.0 12.2% 14.4 Standard 37.7 3.4% 52.3 7.1% 14.6 polyester CF4 coated 41.0 1.6% 49.6  7.5% 8.6 polyester FEP100 39.0 3.2% 48.1  6.8% 9.1

[0052] Table 2 demonstrates the improvement in the consistency of eachdose administered and a reduction in increase of dose through the lifeof the inhaler using inhalers according to the invention.

EXAMPLE 2

[0053] The EOU interior valve deposition and dosing profile on valveswas investigated with PTFE/acetal polymer metering chambers. FluticasonePropionate/Propellant HFA134a Inhalers, 50 microgram, 120 actuation weremanufactured using the DF60 valve and DF60 valve modified with5%PTFE/acetal in the metering chamber. The inhalers were stored for aminimum of 2 weeks before analysis. The deposition and dosing data arepresented in Tables 3 and 4. TABLE 3 EOU Interior Valve Drug DepositionValve type Amount of fluticasone propionate deposited (mg) StandardValve 0.44 Valve modified 0.32 with 5% PTFE/acetal

[0054] The valve according to the invention demonstrates significantlylower interior valve deposition than that seen in the standard valve.This is due to the 5%PTFE/acetal polymer metering chamber havingfluorine at the surface. TABLE 4 Dosing Data Beginning of Use Dose Endof Use Increase in dose (mcg) Dose (mcg) during life of Valve type MeanSD (%) Mean SD (%) inhaler (mcg) Standard 40.5 4.1 53.0 7.6 12.5 ValveModified 42.6 2.2 51.4 7.1 8.8 Valve

[0055] Several experiments were conducted to investigate the quantity ofdrug deposited on different types of polymer blocks.

[0056] The following method was used to analyse the quantity of drugdeposited on the polymer blocks for each experiment. Firstly, thefluticasone propionate suspension was evacuated quickly by piercing theMDI can. The valve was then cut from the MDI and the polymer blockcarefully removed for washing. The polymer block was washedquantitatively with acetonitrile into a 50 ml volumetric flaskcontaining 25 ml water. The drug solution was made to volume and theresultant solution assayed for fluticasone propionate by HPLC.

EXAMPLE 3

[0057] The effect of different polymers on the quantity of drugdeposited was investigated. The polymer blocks used had the standardinjection moulded finish. The polymer blocks were cut to an appropriatesize to fit an 8 ml-inhaler can. The polymer blocks were then placedinto MDI containing a suspension of 0.35% w/w fluticasone propionate in12 g of propellant HFA134a. The inhalers were stored for a minimum of 2weeks before analysis of the drug deposited on the polymer blocks. Thedata are presented in Tables 5 and 6. TABLE 5 Effect of Polymer Used onDrug Deposition Amount of fluticasone propionate Polymer Used deposited(mg) Acetal 0.23 Hostaform C9021TF 0.15 (20% PTFE/acetal blend) THV200G0.14 (TFE, HFP, vinylidene fluoride) THV500G 0.09 (TFE, HFP, vinylidenefluoride) PFA6515N 0.05 (perfluoroalkoxy) FEP6107 0.04 (fluorinatedethylenepropylene) ETFE ET6125 0.04 (ethylenetetrafluoroethylene)

[0058] TABLE 6 Effect of Polymer Used on Drug Deposition Amount offluticasone propionate Polymer Used deposited (mg) Polyester 0.70Polyester/PTFE (LNP WL4040) 0.49

[0059] The addition of PTFE to polyester reduces the fluticasonedeposition significantly compared to pure polyester.

[0060] The lowest levels of drug deposition are seen with the polymerswith the greater levels of fluorination (PFA, ETFE, and FEP).

EXAMPLE 4

[0061] The effect of fluorine coating the polymer and the quantity ofdrug deposited was investigated. Acetal was the polymer coated withfluorine. The coating process was the conventionally known plasmacoating process.

[0062] The polymer blocks were cut to an appropriate size to fit an 8ml-inhaler can. The polymer blocks were then placed into MDI containinga suspension of 0.34% w/w fluticasone propionate in 12 g of propellantHFA134a. The inhalers were stored for a minimum of 2 weeks beforeanalysis of the drug deposited on the polymer blocks. The data arepresent in Table 7. TABLE 7 Effect of Fluorine Coating on DrugDeposition Amount of fluticasone propionate deposited Polymer Used (mg)Acetal 0.70 CF4 plasma coating/acetal 0.33

[0063] Fluorinating the surface of the acetal by coating has reduced thedrug deposition significantly compared to acetal which does not have afluorinated coating.

[0064] It will be understood that the present disclosure is for thepurpose of illustration only and the invention extends to modifications,variations and improvements thereto which will be within the ordinaryskill of the person skilled in the art.

That which is claimed is:
 1. An aerosol container comprising: a vialbody containing an aerosol formulation of a suspension or solution of amedicament in a hydrogen-containing fluorocarbon liquid propellant, anda valve for dispensing a metered amount of the aerosol formulation peractuation thereof, wherein the valve comprises a valve body defining ametering chamber configured to contain a metered amount of the aerosolformulation for dispensing by the valve, a transfer passage throughwhich the metered amount of the aerosol formulation is able to pass fromthe vial body into the metering chamber, and dispensing means whichenables the metered amount of the aerosol formulation to be dispensedfrom the metering chamber; and wherein the metering chamber is made froma plastics material which is a mixture of a fluorinated polymer and anon-fluorinated polymer.
 2. An aerosol container according to claim 1,wherein the plastics material comprises at least 5% by weightfluorinated polymer.
 3. An aerosol container according to claim 1,wherein a part or all of the surface of said metering chamber which isin contact with the aerosol formulation is coated with a fluorinatedmaterial.
 4. An aerosol container according to claim 3, wherein thecoating is a plasma coating.
 5. An aerosol container according to claim4, wherein the plasma coating is a CF₄ coating.
 6. An aerosol containeraccording to claim 1, wherein the propellant is selected from liquefied1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane, or amixture thereof.
 7. An aerosol container according to claim 6, whereinthe propellant is substantially free of adjuvants.
 8. An aerosolcontainer according to claim 6, wherein the medicament is selected fromfluticasone propionate, salbutamol, beclomethasone dipropionate,salmeterol, pharmaceutically acceptable salts, solvates or estersthereof and mixtures thereof.
 9. An aerosol container according to claim1, wherein the metering chamber is moulded from the plastics material.10. An aerosol container according to claim 1, wherein the fluorinatedpolymer is selected from the group consisting of polytetrafluoroethylene(PTFE), polyvinylfluoride (PVF) and polychlorotrifluoroethylene (PCTFE).11. An aerosol container according to claim 1, wherein thenon-fluorinated polymer is selected from the group consisting of acetaland polyester.
 12. An inhalation device comprising an aerosol container,said aerosol container comprising: a vial body containing an aerosolformulation of a suspension or solution of a medicament in ahydrogen-containing fluorocarbon liquid propellant, and a valve fordispensing a metered amount of the aerosol formulation per actuationthereof, wherein the valve comprises a valve body defining a meteringchamber configured to contain a metered amount of the aerosolformulation for dispensing by the valve, a transfer passage throughwhich the metered amount of the aerosol formulation is able to pass fromthe vial body into the metering chamber, and dispensing means whichenables the metered amount of the aerosol formulation to be dispensedfrom the metering chamber; and wherein the metering chamber is made froma plastics material which is a mixture of a fluorinated polymer and anon-fluorinated polymer.
 13. An inhalation device according to claim 12,wherein the plastics material comprises at least 5% by weightfluorinated polymer.
 14. An inhalation device according to claim 12,wherein a part or all of the surface of said metering chamber which isin contact with the aerosol formulation is coated with a fluorinatedmaterial.
 15. An inhalation device according to claim 14, wherein thecoating is a plasma coating.
 16. An inhalation device according to claim15, wherein the plasma coating is a CF₄ coating.
 17. An inhalationdevice according to claim 12, wherein the metering chamber is mouldedfrom the plastics material.
 18. An inhalation device according to claim12, wherein the fluorinated polymer is selected from the groupconsisting of polytetrafluoroethylene (PTFE), polyvinylfluoride (PVF)and polychlorotrifluoroethylene (PCTFE).
 19. An inhalation deviceaccording to claim 12, wherein the non-fluorinated polymer is selectedfrom the group consisting of acetal and polyester.
 20. An inhalationdevice according to claim 12, wherein the inhalation device is a metereddose inhaler.